TY - JOUR
T1 - Bupropion and naltrexone in methamphetamine use disorder
AU - Trivedi, Madhukar H.
AU - Walker, Robrina
AU - Ling, Walter
AU - dela Cruz, Adriane
AU - Sharma, Gaurav
AU - Carmody, Thomas
AU - Ghitza, Udi E.
AU - Wahle, Aimee
AU - Kim, Mora
AU - Shores-Wilson, Kathy L
AU - Sparenborg, Steven
AU - Coffin, Phillip
AU - Schmitz, Joy
AU - Wiest, Katharina
AU - Bart, Gavin
AU - Sonne, Susan C.
AU - Wakhlu, Sidarth
AU - John Rush, A.
AU - Nunes, Edward V.
AU - Shoptaw, Steven
N1 - Funding Information:
Supported by awards (UG1DA020024 [to Dr. Trivedi], UG1DA013035 [to Dr. Nunes], UG1DA040316, UG1DA013727, and UG1DA015815) from the National Institute on Drug Abuse (NIDA) of the National Institutes of Health; and by the Department of Health and Human Services under contract numbers HHSN271201500065C (Clinical Coordinating Center, the Emmes Company) and HHSN271201400028C (Data and Statistics Center, the Emmes Company). Alkermes provided Vivitrol (naltrexone for extended-release injectable suspension) and matched placebo free of charge for use in this trial under a written agreement with NIDA.
Publisher Copyright:
Copyright © 2021 Massachusetts Medical Society.
PY - 2021/1/14
Y1 - 2021/1/14
N2 - BACKGROUND The use of naltrexone plus bupropion to treat methamphetamine use disorder has not been well studied. METHODS We conducted this multisite, double-blind, two-stage, placebo-controlled trial with the use of a sequential parallel comparison design to evaluate the efficacy and safety of extended-release injectable naltrexone (380 mg every 3 weeks) plus oral extended-release bupropion (450 mg per day) in adults with moderate or severe methamphetamine use disorder. In the first stage of the trial, participants were randomly assigned in a 0.26:0.74 ratio to receive naltrexone-bupropion or matching injectable and oral placebo for 6 weeks. Those in the placebo group who did not have a response in stage 1 underwent rerandomization in stage 2 and were assigned in a 1:1 ratio to receive naltrexone-bupropion or placebo for an additional 6 weeks. Urine samples were obtained from participants twice weekly. The primary outcome was a response, defined as at least three methampheta mine negative urine samples out of four samples obtained at the end of stage 1 or stage 2, and the weighted average of the responses in the two stages is reported. The treatment effect was defined as the between-group difference in the overall weighted responses. RESULTS A total of 403 participants were enrolled in stage 1, and 225 in stage 2. In the first stage, 18 of 109 participants (16.5%) in the naltrexone-bupropion group and 10 of 294 (3.4%) in the placebo group had a response. In the second stage, 13 of 114 (11.4%) in the naltrexone-bupropion group and 2 of 111 (1.8%) in the placebo group had a response. The weighted average response across the two stages was 13.6% with naltrexone-bupropion and 2.5% with placebo, for an overall treatment effect of 11.1 percentage points (Wald z-test statistic, 4.53; P<0.001). Adverse events with naltrexone-bupropion included gastrointestinal disorders, tremor, malaise, hyperhidrosis, and anorexia. Serious adverse events occurred in 8 of 223 participants (3.6%) who received naltrexone-bupropion during the trial. CONCLUSIONS Among adults with methamphetamine use disorder, the response over a period of 12 weeks among participants who received extended-release injectable naltrexone plus oral extended-release bupropion was low but was higher than that among participants who received placebo. (Funded by the National Institute on Drug Abuse and others; ADAPT-2 ClinicalTrials.gov number, NCT03078075.).
AB - BACKGROUND The use of naltrexone plus bupropion to treat methamphetamine use disorder has not been well studied. METHODS We conducted this multisite, double-blind, two-stage, placebo-controlled trial with the use of a sequential parallel comparison design to evaluate the efficacy and safety of extended-release injectable naltrexone (380 mg every 3 weeks) plus oral extended-release bupropion (450 mg per day) in adults with moderate or severe methamphetamine use disorder. In the first stage of the trial, participants were randomly assigned in a 0.26:0.74 ratio to receive naltrexone-bupropion or matching injectable and oral placebo for 6 weeks. Those in the placebo group who did not have a response in stage 1 underwent rerandomization in stage 2 and were assigned in a 1:1 ratio to receive naltrexone-bupropion or placebo for an additional 6 weeks. Urine samples were obtained from participants twice weekly. The primary outcome was a response, defined as at least three methampheta mine negative urine samples out of four samples obtained at the end of stage 1 or stage 2, and the weighted average of the responses in the two stages is reported. The treatment effect was defined as the between-group difference in the overall weighted responses. RESULTS A total of 403 participants were enrolled in stage 1, and 225 in stage 2. In the first stage, 18 of 109 participants (16.5%) in the naltrexone-bupropion group and 10 of 294 (3.4%) in the placebo group had a response. In the second stage, 13 of 114 (11.4%) in the naltrexone-bupropion group and 2 of 111 (1.8%) in the placebo group had a response. The weighted average response across the two stages was 13.6% with naltrexone-bupropion and 2.5% with placebo, for an overall treatment effect of 11.1 percentage points (Wald z-test statistic, 4.53; P<0.001). Adverse events with naltrexone-bupropion included gastrointestinal disorders, tremor, malaise, hyperhidrosis, and anorexia. Serious adverse events occurred in 8 of 223 participants (3.6%) who received naltrexone-bupropion during the trial. CONCLUSIONS Among adults with methamphetamine use disorder, the response over a period of 12 weeks among participants who received extended-release injectable naltrexone plus oral extended-release bupropion was low but was higher than that among participants who received placebo. (Funded by the National Institute on Drug Abuse and others; ADAPT-2 ClinicalTrials.gov number, NCT03078075.).
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U2 - 10.1056/NEJMoa2020214
DO - 10.1056/NEJMoa2020214
M3 - Article
C2 - 33497547
AN - SCOPUS:85099741272
VL - 384
SP - 140
EP - 153
JO - New England Journal of Medicine
JF - New England Journal of Medicine
SN - 0028-4793
IS - 2
ER -